The long term goal of this project is to identify some of the mechanisms that are responsible for brain amino acid uptake, particularly those that are active at the blood-brain barrier and at the barrier between the blood and cerebrospinal fluid. The project is mainly directed towards the exploration of the role of glutathione in the functioning of transport processes. The amino acid uptake of isolated brain capillaries and of the choroid plexus will be determined. The specificity of the uptake and the requirements for transport will be studied. The relationship of the glutathione to transport will be studied by determining the uptake capacity of preparations that were depleted in intracellular glutathione by the administration of inhibitors of biosynthesis of this tripeptide. The possible involvement of gamma-glutamyl transpeptidase in transport will be studied by determining the specificity of this enzyme in its interaction with amino acids. Studies are also carried out on the mechanism of conclusive action of allylglycine, an analog of cysteine, which is likely to interfere with glutathione synthess or the metabolism and transport of sulfur containing amino acids.